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- W3201143744 endingPage "103149" @default.
- W3201143744 startingPage "103149" @default.
- W3201143744 abstract "Deconstructing tissue-specific effects of genes and variants on proliferation is critical to understanding cellular transformation and systematically selecting cancer therapeutics. This requires scalable methods for multiplexed genetic screens tracking fitness across time, across lineages, and in a suitable niche, since physiological cues influence functional differences. Towards this, we present an approach, coupling single-cell cancer driver screens in teratomas with hit enrichment by serial teratoma reinjection, to simultaneously screen drivers across multiple lineages in vivo. Using this system, we analyzed population shifts and lineage-specific enrichment for 51 cancer associated genes and variants, profiling over 100,000 cells spanning over 20 lineages, across two rounds of serial reinjection. We confirmed that c-MYC alone or combined with myristoylated AKT1 potently drives proliferation in progenitor neural lineages, demonstrating signatures of malignancy. Additionally, mutant MEK1S218D/S222D provides a proliferative advantage in mesenchymal lineages like fibroblasts. Our method provides a powerful platform for multi-lineage longitudinal study of oncogenesis." @default.
- W3201143744 created "2021-09-27" @default.
- W3201143744 creator A5006750757 @default.
- W3201143744 creator A5016038041 @default.
- W3201143744 creator A5018324826 @default.
- W3201143744 creator A5026337156 @default.
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- W3201143744 creator A5059024686 @default.
- W3201143744 creator A5081769400 @default.
- W3201143744 creator A5085886455 @default.
- W3201143744 date "2021-10-01" @default.
- W3201143744 modified "2023-10-15" @default.
- W3201143744 title "Charting oncogenicity of genes and variants across lineages via multiplexed screens in teratomas" @default.
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